[Simultaneous determination and pharmacokinetic study of five compounds from total extract of Clinopodium chinense in abnormal uterine bleeding rat plasma by UPLC-MS/MS]

Zhongguo Zhong Yao Za Zhi. 2022 Sep;47(18):5071-5078. doi: 10.19540/j.cnki.cjcmm.20220421.702.
[Article in Chinese]

Abstract

Clinopodium chinense, a traditional folk medicinal herb, has been used to treat abnormal uterine bleeding(AUB) for many years. Saponins and flavonoids are the main active components in C. chinense. To study the pharmacokine-tics of multiple components from the total extract of C. chinense(TEC), we established a sensitive and rapid method of ultra-perfor-mance liquid chromatography coupled with tandem mass spectrometry(UPLC-MS/MS) for simultaneous determination of five compounds in the plasma of AUB rats. After validation, the AUB model was established with SD female rats which got pregnant on the same day by gavage with mifepristone(12.4 mg·kg~(-1)) and misoprostol(130 μg·kg~(-1)). The established method was applied to the detection of hesperidin, naringenin, apigenin, saikosaponin a, and buddlejasaponin Ⅳb in AUB rats after the administration of TEC. The pharmacokinetic parameters were calculated by DAS 2.0. The five compounds showed good linear relationship within the detection range. The specificity, accuracy, precision, recovery, matrix effect, and stability of the method all matched the requirements of biolo-gical sample detection. The above 5 compounds were detected in the plasma of AUB rats after the administration of TEC. The C_(max) va-lues of hesperidin, naringenin, apigenin, saikosaponin a, and clinoposide A were 701.6, 429.5, 860.7, 75.1, and 304.1 ng·mL~(-1), respectively. All the compounds owned short half-life and quick elimination rate in vivo, and the large apparent volume of distribution indicated that they were widely distributed in tissues. Being rapid, accurate, and sensitive, this method is suitable for the pharmacokinetic study of extracts of Chinese herbal medicines and provides a reference for the study of pharmacodynamic material basis of C. chinense in treating AUB.

Keywords: Clinopodium chinense; UPLC-MS/MS; abnormal uterine bleeding; pharmacokinetics; total extract.

MeSH terms

  • Administration, Oral
  • Animals
  • Apigenin / analysis
  • Chromatography, High Pressure Liquid / methods
  • Chromatography, Liquid
  • Drugs, Chinese Herbal* / chemistry
  • Female
  • Flavonoids / analysis
  • Hesperidin*
  • Lamiaceae*
  • Mifepristone
  • Misoprostol*
  • Oleanolic Acid / analogs & derivatives
  • Plant Extracts / chemistry
  • Rats
  • Saponins*
  • Tandem Mass Spectrometry / methods
  • Uterine Hemorrhage

Substances

  • Drugs, Chinese Herbal
  • Flavonoids
  • Plant Extracts
  • Saponins
  • Misoprostol
  • Mifepristone
  • Oleanolic Acid
  • Apigenin
  • Hesperidin
  • saikosaponin D